External control of internal movement: vesicle trafficking regulation by heterotrimeric G proteins

CORIA, ANDREA SOLEDAD; MASSERONI, MARÍA LUJÁN; DÍAZ AÑEL, ALBERTO MARCELO

Los Cocos, Córdoba, Argentina

Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine; 2010

Universidad de Buenos Aires, NIH, UMass

Until a few years ago, it was thought that generation of transport carriers at the Trans-Golgi Network (TGN) had no regulation, hence its definition as “constitutive trafficking”. In our laboratory we have described a new trafficking regulatory pathway, required to manage protein secretion accordingly to the cell requirements. A key member of this signal transduction pathway is Protein Kinase D1 (PKD1). This kinase, when activated, is capable of translocate to TGN in order to regulate vesicle fission through the phosphorylation of currently unknown effectors. We have found that PKD1-dependent trafficking regulation is initiated at the plasma membrane by members of heterotrimeric GTP-binding proteins, particularly alpha subunits of Gq family and two specific betagamma subunits combinations, beta1gamma2 and beta3gamma2. Both G proteins subunits, alpha and betagamma, activate Phospholipases Cbeta (PLCbeta), which produce Diacylglycerol (DAG), that recruits PKD1 to the TGN and activates members of the novel Protein Kinase C (nPKC) subfamily. These PKCs phosphorylate PKD1 at the TGN, thus initiating membrane fission. New challenges arise from these results in order to complete this pathway, among them the characterization of G Protein Coupled Receptors linking external signals with intracellular protein trafficking regulation.